ArticleThe Journal of biological chemistry2016
Reactive Center Loop (RCL) Peptides Derived from Serpins Display Independent Coagulation and Immune Modulating Activities.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 49 citations in OpenAlex.
- Peptides Derived From Reactive Center Loops Inhibit Digestive Trypsin-Like Enzymes in Lepidopteran Pests.Archives of insect biochemistry and physiology · 2026Article
- Host cell and viral protease targets of human SERPINs identified by in silico docking.The EMBO journal · 2025Article
- Proteomics of Bacterial and Mouse Extracellular Vesicles Released in the Gastrointestinal Tracts of Nutrient-Stressed Animals Reveals an Interplay Between Microbial Serine Proteases and Mammalian Serine Protease Inhibitors.International journal of molecular sciences · 2025Article
- The role of coagulome in the tumor immune microenvironment.Advanced drug delivery reviews · 2023Review
- Review on Extraction, Modification, and Synthesis of Natural Peptides and Their Beneficial Effects on Skin.Molecules (Basel, Switzerland) · 2023Review
- Tissue Specific Dual RNA-Seq Defines Host-Parasite Interplay in Murine Visceral Leishmaniasis Caused by Leishmania donovani and Leishmania infantum.Microbiology spectrum · 2022Article
- Neuroserpin: structure, function, physiology and pathology.Cellular and molecular life sciences : CMLS · 2021Review
- Myxomavirus serpin alters macrophage function and prevents diffuse alveolar hemorrhage in pristane-induced lupus.Clinical immunology (Orlando, Fla.) · 2021Article
- A Novel Mouse Monoclonal Antibody C42 against C-Terminal Peptide of Alpha-1-Antitrypsin.International journal of molecular sciences · 2021Article
- Serine Proteases and Chemokines in Neurotrauma: New Targets for Immune Modulating Therapeutics in Spinal Cord Injury.Current neuropharmacology · 2021Review
- Therapeutic SERPINs: Improving on Nature.Frontiers in cardiovascular medicine · 2021Review
- Fibrinolytic Serine Proteases, Therapeutic Serpins and Inflammation: Fire Dancers and Firestorms.Frontiers in cardiovascular medicine · 2021Review
- RecombinantPharmaceutics · 2020Article
- Peptides based on the reactive center loop of Manduca sexta serpin-3 block its protease inhibitory function.Scientific reports · 2020Article
- Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function.Journal of clinical medicine · 2020Article
- Deriving Immune Modulating Drugs from Viruses-A New Class of Biologics.Journal of clinical medicine · 2020Review
- Immune protection is dependent on the gut microbiome in a lethal mouse gammaherpesviral infection.Scientific reports · 2020Article
- The immunosuppressive functions of two novel tick serpins, HlSerpin-a and HlSerpin-b, from Haemaphysalis longicornis.Immunology · 2020Article
- Article
- Serp-2, a virus-derived apoptosis and inflammasome inhibitor, attenuates liver ischemia-reperfusion injury in mice.Journal of inflammation (London, England) · 2019Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Serpins regulate coagulation and inflammation, binding serine proteases in suicide-inhibitory complexes. Target proteases cleave the serpin reactive center loop scissile P1-P1' bond, resulting in serpin-protease suicide-inhibitory complexes. This inhibition requires a near full-length serpin sequence. Myxomavirus Serp-1 inhibits thrombolytic and thrombotic proteases, whereas mammalian neuroserpin (NSP) inhibits only thrombolytic proteases. Both serpins markedly reduce arterial inflammation and plaque in rodent models after single dose infusion. In contrast, Serp-1 but not NSP improves survival in a lethal murine gammaherpesvirus68 (MHV68) infection in interferon γ-receptor-deficient mice (IFNγR(-/-)). Serp-1 has also been successfully tested in a Phase 2a clinical trial. We postulated that proteolytic cleavage of the reactive center loop produces active peptide derivatives with expanded function. Eight peptides encompassing predicted protease cleavage sites for Serp-1 and NSP were synthesized and tested for inhibitory function in vitro and in vivo. In engrafted aorta, selected peptides containing Arg or Arg-Asn, not Arg-Met, with a 0 or +1 charge, significantly reduced plaque. Conversely, S-6 a hydrophobic peptide of NSP, lacking Arg or Arg-Asn with -4 charge, induced early thrombosis and mortality. S-1 and S-6 also significantly reduced CD11b(+) monocyte counts in mouse splenocytes. S-1 peptide had increased efficacy in plasminogen activator inhibitor-1 serpin-deficient transplants. Plaque reduction correlated with mononuclear cell activation. In a separate study, Serp-1 peptide S-7 improved survival in the MHV68 vasculitis model, whereas an inverse S-7 peptide was inactive. Reactive center peptides derived from Serp-1 and NSP with suitable charge and hydrophobicity have the potential to extend immunomodulatory functions of serpins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.